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Prostaglandin F2α (PGF2α) is luteolytic in a number of species and the recent finding of endogenous secretion of PGF2α into the utero—ovarian vein of oestrogen-treated guinea-pigs (Blatchley, Donovan, Poyser, Horton, Thompson & Los, 1971) supports the hypothesis that PGF2α is the uterine luteolytic factor. Because the luteolytic effect of the uterus on the corpus luteum is local, it is necessary that a luteolysin secreted by one uterine horn can cause regression of the corpus luteum on the same side. The present experiments were designed to investigate the effect of PGF2α infused into the ovarian artery or uterine vein of the cyclic ewe.
Polyvinyl catheters (o.d. 0·8 mm) were inserted into a branch of one ovarian artery and a branch of the uterine vein on the same side in Merino ewes. The other ovary was removed. On day 6, 7, 8 or 9 of the succeeding
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ABSTRACT
The subcellular distribution and compartmentalization of choriomammotrophin (CM) and progesterone within ovine placentomes was investigated using differential and density gradient centrifugation techniques. Approximately 67% of placental CM and 45% of progesterone was associated with subcellular particles. The 10 000 g particulate fraction contained the highest specific activity of both CM and progesterone (19·1 ±3·8 (s.e.m.) μg/mg and 71·5 ± 9·2 pmol/mg protein respectively). This fraction was also shown to contain electron-dense granules with morphology similar to that of hormone-containing secretory granules isolated from other endocrine tissues. Particle-associated CM sedimented to a density of 1·051–1·054 g/ml in colloidal silica gradients and displayed physicochemical characteristics consistent with its storage in secretory granules. During in-vitro incubations, particle-associated CM was stable for up to 90 min, but dissociated when incubated in hypoosmotic medium. Particulate progesterone, which was also present in the CM-rich fraction and was stable for up to 90 min of incubation, was not affected by decreasing the osmolality of the incubation medium. These data suggest that ovine CM (but not progesterone) is stored within a population of secretory granules located within placentomes.
J. Endocr. (1986) 111, 217–223
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SUMMARY
Thyroid glands were surgically ablated from foetal sheep between 81 and 96 days of gestation in order to study the role of the thyroid gland in foetal development. Gestation of ewes bearing thyroidectomized foetuses was prolonged by about 5 days, and athyroid lambs failed to survive more than 24 h. Athyroid foetuses delivered by Caesarian section 1 week before term were characterized by low body weight, low thymus gland weight, and shortened limbs. Foetal thyroidectomy markedly retarded both the maturation and growth of wool follicles and osseous tissue.
Plasma concentrations of growth hormone, calcium and phosphorus were normal in the athyroid foetuses, but cholesterol levels were increased. The absence of thyroxine in the foetal circulation agrees with previous findings that the ovine placenta is impermeable to maternal thyroxine.
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Prolonged pregnancy following foetal hypophysectomy or adrenalectomy (Liggins, Kennedy & Holm, 1967; Drost & Holm, 1968) and premature parturition following injection of corticotrophin or corticosteroids into the ovine foetus (Van Rensburg, 1967; Halliday & Buttle, 1968; Liggins, 1968) implicate the foetal adrenal cortex in the initiation of parturition in sheep. Consequently, foetal plasma corticosteroid concentrations and corticosteroid secretion by the foetal adrenal should be greatly increased towards term. Observations during acute studies on anaesthetized sheep suggest this (Alexander, Britton, James, Nixon, Parker, Wintour & Wright, 1968), but there is no information about blood concentrations or secretion rates of corticosteroids in normal undisturbed sheep foetuses in utero.
We cannulated the carotid artery and the facial branch of the jugular vein of four single Merino foetuses with polyvinyl chloride tubing (o.d. 1·27 mm., i.d. 0·86 mm.) with the ewes under general anaesthesia (pentobarbitone sodium (20 mg./kg., i.v.) followed by halothane and oxygen).
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SUMMARY
Foetal lambs (100–150 days' gestation) with indwelling vascular catheters were used to study the regulation of the insulin concentration in the plasma of foetal lambs in utero. Immediately after the implantation of the catheters the insulin concentration in foetal plasma was significantly correlated with the foetal glucose and fructose concentrations and with the maternal glucose concentration. On the next day the foetal insulin concentration was significantly correlated only with the maternal glucose concentration.
Both glucose and fructose, when infused i.v., increased the insulin concentration in foetal plasma, but the increases were slow and far less than those observed in newborn lambs infused with glucose or fructose. Intravenous infusion of isoprenaline or glucagon did not alter the plasma insulin concentration of foetal lambs, but both caused a rapid increase in the insulin concentration of newborn lambs. Glucagon did not potentiate the insulin response to glucose. Addition of aminophylline to a glucagon infusion failed to cause insulin secretion in foetal lambs. The results suggest the cyclic-3′,5′-AMP dependent part of the insulin secretory mechanism does not develop fully before the last week of gestation.
Gel filtration of foetal plasma on Sephadex indicated that the immunoreactive material present was insulin. No significant amounts of proinsulin were found.
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SUMMARY
The ovarian and part of the uterine venous drainage was diverted through the superficial anterior mammary vein leaving the ovary in its normal position and preserving utero—ovarian relationships. The operation has been performed successfully in 18 pregnant Merino ewes (70–120 days' gestation). Blood samples were collected by direct puncture of the mammary and jugular veins during the latter half of pregnancy and the subsequent breeding season. All ewes lambed normally after a gestation period of 146–151 days. Twelve of the 16 surviving ewes resumed cyclic oestrous behaviour. Plasma progesterone concentration was measured by a competitive proteinbinding assay. Utero—ovarian venous blood flow and rates of ovarian progesterone secretion were measured throughout the oestrous cycle. Progesterone secretion during the luteal phase of the cycle was in the range of 4·5–6·0 mg/day. The progesterone concentrations in peripheral plasma were similar to those found in normal ewes.
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SUMMARY
Progesterone concentrations in the peripheral plasma of goats were measured by a protein-binding assay. The mean concentration was extremely low on the day of oestrus (0·2 ng/ml) and was not significantly different from that found in anoestrous or ovariectomized animals. The concentration increased to a maximum of 4 ng/ml on about day 10 of the 21-day cycle, and decreased rapidly during the last 3 days of the cycle.
Plasma progesterone concentration during early pregnancy (2·5–3·5 ng/ml) was similar to the luteal phase value and remained steady from day 8 to day 60. Between days 60 and 70 there was a secondary increase in progesterone concentration which was maintained at this increased level (4·5–5·5 ng/ml) until just before parturition. In twin-bearing animals, the secondary increase was greater. Progesterone concentration decreased rapidly during the 1–2 days preceding parturition, but the concentration was still quite high on the day of parturition (1·25 ng/ml).
The progesterone concentration in peripheral plasma was markedly increased during anaesthesia and the operation. After bilateral ovariectomy of the pregnant goat, peripheral progesterone concentration fell rapidly from 9 to 2·5 ng/ml during the first ½ h and then more slowly during the next 5–6 h. The animals aborted 36–48 h later.
A consistent positive arterio—venous difference for progesterone was observed across the pregnant uterus in two unanaesthetized goats. These results indicate that the ovary is the main site of progesterone production in the pregnant goat and that production by the placenta is small and unlikely to influence the level of this hormone in the maternal circulation.
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The retardation of growth and maturation of the thyroidectomized foetal lamb suggests that maternal thyroid hormone does not cross the ovine placenta in sufficient quantities to permit normal foetal development (Hopkins & Thorburn, 1970). Assessments of the permeability of the ewe's placenta to thyroxine (T4) have previously been undertaken using labelled hormone. Dussault & Fisher (1970) found no evidence of placental transfer, although other workers have concluded that transfer does occur (Comline, Nathanielsz & Silver, 1970; Burrow, Anderson & Quilligan, 1969). Long-term studies investigating the transport of unlabelled T4 have not been reported. The aim of the present study was to investigate the transfer of maternal T4 across the placenta of the ewe during the last 6 weeks of pregnancy.
Surgical thyroidectomy was performed on two foetal lambs of approximately 110 days' gestation. Indwelling carotid catheters (1·5 mm o.d., 1·0 mm i.d.) inserted at the time of
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SUMMARY
Relationships between foetal corticosteroid concentrations, utero-ovarian prostaglandin F (PGF) and maternal peripheral progesterone have been examined in detail in goats shortly before spontaneous parturition at term. Foetal corticosteroids increased during the last 13-11 days of gestation and particularly sharply during the last 3 days and even during advanced labour. About 24 h before parturition, acute releases of PGF were evident in the vein draining the pregnant uterine horn, and these corresponded closely to the time of luteal regression. Further release of PGF occurred when progesterone declined to low levels, probably reflecting the course of labour.
The changes observed before premature parturition, induced by infusing ACTH into foetal goats, were similar except for the more rapid increase in foetal corticosteroid concentrations. Immature neonates born after ACTH treatment were viable, placental delivery was normal and lactogenesis occurred in the mothers indicating that the treatment promoted full expression of the critical perinatal events. The early, acute releases of PGF were ipsilateral to the ACTH-infused foetus and were luteolytic provided the corpora lutea were also on that side. Luteolysis failed or was abnormally delayed if the corpora lutea were contralateral and prolonged ACTH treatment of the foetuses in such cases caused foetal death probably because of premature failure of the placenta. Similar findings were noted if ACTH infusion of the foetus was accompanied by simultaneous progesterone treatment of the mothers in order to block the induction of labour. It was suggested that placental changes occurring during foetal hypercortisolism might be caused by increased placental oestrogen synthesis and the effect of this on the foeto-maternal junction along with a stimulatory action on PG synthesis in the maternal placenta. Experimental disruption of the normal sequence of events, when labour was blocked by progesterone, proved to be lethal to the foetus if the loss of placental integrity progressed sufficiently.
The chain of regulatory signals linking increased activity of the foetal adrenal with parturition thus appears to involve stimulation of oestrogen biosynthesis, PGF release from the maternal placenta and the start of physical changes at the placental junction. Provided the foetus and corpora lutea are ipsilateral, the early releases of PGF effect luteolysis and a withdrawal of progesterone from the maternal circulation. When progesterone concentrations are sufficiently low, labour is initiated and its progress reflected by further release of PGF. The control mechanisms, which also provide for the final maturation of the foetus, clearly enable a close synchronization of the various perinatal events which are essential for the transition from foetal to postnatal life.
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ABSTRACT
Groups of three goats at 50, 90 and 130 days of gestation were passively immunized against ovine LH (oLH) by i.v. infusion of 8 ml serum equivalent of the immunoglobulin fraction of rabbit anti-oLH serum (LHAS). Goats at the same stages of gestation as above served as controls and received 8 ml serum equivalent of the immunoglobulin fraction of normal rabbit serum (NRS). Plasma concentrations of progesterone were determined by specific radioimmunoassay of blood collected at 20-min intervals from 6 h before infusion of LHAS or NRS to 12 h after infusion. Less frequent sampling was performed from 2 days before to 6 days after infusion. Plasma from all LHAS-immunized goats exhibited binding of oLH. Twelve hours after immunization, titres ranged from 1:135 to 1:215. All LHAS-treated goats had titres of less than 1:10 by 5 days after immunization, but a low level of oLH binding was still detectable. Treatment with LHAS or NRS did not shorten the length of gestation, with all goats delivering live offspring between 142 and 147 days after conception. Plasma concentrations of LH ranged from less than 0·15 μg/l to 4·8 μg/l and were greater than 0·15 μg/l in 181 of 255 samples (71%) for both the NRS-treated group, throughout the experiment, and the LHAS-treated groups before infusion of antiserum. Luteinizing hormone was not detectable in plasma samples obtained after LHAS infusion in goats at 50 or 130 days of pregnancy. Plasma concentrations of LH exceeded 0·15 μg/l in only five of 51 (10%) samples in 90-day-pregnant goats treated with LHAS, the maximum value reached being 0·80 μg/l.
Plasma concentrations of progesterone did not alter significantly after infusion of LHAS or NRS at 50, 90 or 130 days of gestation, nor were they significantly different between the groups treated with LHAS and NRS.
The role of LH in the maintenance of pregnancy in the goat after 50 days of gestation is questioned.
J. Endocr. (1987) 114, 413–436
